Diversity-oriented synthesis and cytotoxic activity evaluation of biaryl-containing macrocycles

Pérez-Labrada, Karell; Cruz-Mendoza, Marco A.; Chávez‐Riveros, Alejandra; Hernández‐Vázquez, Eduardo; Torroba, Tomás; Miranda, Luis D.

doi:10.1039/c6ob02726a

Cited by 11 publications

(6 citation statements)

References 51 publications

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“…One set contained poly-azaheterocycles ( Scheme 1A ) such as benzopyrrolizidines (1) ( Miranda and Hernández-Vázquez, 2015 ), pyrazinoisoquinolines (2) ( Hernández-Vázquez and Miranda, 2016 ), peptidic pyrazinones (3) ( Hernández-Vázquez et al., 2019 ), acyclic diphenylamines (4) ( Chávez-Riveros et al., 2021 ), and isoindolones (5) ( Icelo-Ávila et al., 2017 ). The second set consisted of bis (aryl ether)cyclophanes (6) ( Hernández-Vázquez et al., 2018 ) and biphenyl-containing macrocycles (7) ( Pérez-Labrada et al., 2017 ). The structures of the chemical collection are shown in Supporting Information ( Tables S1 – S7 ).…”

Section: Resultsmentioning

confidence: 99%

Discovery of Benzopyrrolizidines as Promising Antigiardiasic Agents

Auriostigue-Bautista

Hernández‐Vázquez

González-Calderón

et al. 2022

Front. Cell. Infect. Microbiol.

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Current treatments for giardiasis include drugs with undesirable side effects, which increase the levels of therapeutic desertion and promote drug resistance in the parasites. Herein, we describe the antigiardiasic evaluation on Giardia lamblia trophozoites of a structurally diverse collection of 74 molecules. Among these scaffolds, we discovered a benzopyrrolizidine derivative with higher antigiardiasic activity (IC50 = 11 µM) and lower cytotoxicity in human cell cultures (IC50 = 130 µM) than those displayed by the current gold-standard drugs (metronidazole and tinidazole). Furthermore, this compound produced morphologic modifications of trophozoites, with occasional loss of one of the nuclei, among other changes not observed with standard giardicidal drugs, suggesting that it might act through a novel mechanism of action.

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Section: Resultsmentioning

confidence: 99%

Discovery of Benzopyrrolizidines as Promising Antigiardiasic Agents

Auriostigue-Bautista

Hernández‐Vázquez

González-Calderón

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Having in hand the collection of diversely decorated macrocycles, we proceeded to evaluate their potential cytotoxic effect toward a set of six cancerous cell lines plus one noncancerous line. This line of inquiry was based on the observation that several macrocyclic structures exhibited relevant cytotoxic and anticancer properties . Therefore, the macrocycles containing 20 members were first subjected to a preliminary cytotoxic screening to distinguish further between active and nonactive derivatives.…”

Section: Resultsmentioning

confidence: 99%

“…This line of inquiry was based on the observation that several macrocyclic structures exhibited relevant cytotoxic and anticancerp roperties. [10][11][12]20] Therefore, the macrocyclesc ontaining 20 members weref irst subjected to ap reliminaryc ytotoxic screening to distinguish further betweena ctive and nonactive derivatives. As the concentration of 50 mm was employed by our group for this purpose, [15] we initiated the screening with this level of each compound (n = 2).…”

Section: Cytotoxic Evaluation and Sar Analysismentioning

confidence: 99%

Cytotoxic Activity and Structure–Activity Relationship of Triazole‐Containing Bis(Aryl Ether) Macrocycles

et al. 2018

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Cancer continues to be a worldwide health problem. Certain macrocyclic molecules have become attractive therapeutic alternatives for this disease because of their efficacy and, frequently, their novel mechanisms of action. Herein, we report the synthesis of a series of 20-, 21-, and 22-membered macrocycles containing triazole and bis(aryl ether) moieties. The compounds were prepared by a multicomponent approach from readily available commercial substrates. Notably, some of the compounds displayed interesting cytotoxicity against cancer (PC-3) and breast (MCF-7) cell lines, especially those bearing an aliphatic or a trifluoromethyl substituent on the N-phenyl moiety (IC <13 μm). Additionally, some of the compounds were able to induce apoptosis relative to the solvent control; in particular, (Z)-N-cyclohexyl-7-oxo-6-[4-(trifluoromethyl)phenyl]-1 H-3,10-dioxa-6-aza-1(4,1)-triazola-4(1,3),9(1,4)-dibenzenacyclotridecaphane-5-carboxamide (12 f) was the most potent in this regard (22.7 % of apoptosis).

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“…Finally, the cytotoxic activity of the formed biarylcontaining macrocycles 140 was examined and compared with Etoposide as a reference anticancer drug, and three of them showed activities against leukemia, glioblastoma, and lung cancer cell lines (IC 50 = 4.0, 5.9, and 7.6, respectively). [76] Scheme 45. Synthesis of benzodiazepinediones.…”

Section: Chemistryselectmentioning

confidence: 99%

Annulation of the Ugi Products Using Palladium Catalysts

2022

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For almost half a century of efforts to make them, the importance of Ugi products has substantially expanded because they are used as precursors for the synthesis of more complex structures, such as peptides, amino acids, pharmaceutical compounds, and heterocycles. Through the introduction of a double or triple bond along with a carbon‐halide bond in the starting materials, the Ugi adduct can be cyclized through Pd‐catalyzed intramolecular reactions to create sophisticated heterocycles. This article discusses the role of palladium in the catalytic cyclization of the Ugi adducts and covers the published research from 2000 to 2022. Moreover, the proposed mechanisms of Pd‐catalyzed annulation of Ugi adducts are also reviewed.

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Diversity-oriented synthesis and cytotoxic activity evaluation of biaryl-containing macrocycles

Cited by 11 publications

References 51 publications

Discovery of Benzopyrrolizidines as Promising Antigiardiasic Agents

Discovery of Benzopyrrolizidines as Promising Antigiardiasic Agents

Cytotoxic Activity and Structure–Activity Relationship of Triazole‐Containing Bis(Aryl Ether) Macrocycles

Annulation of the Ugi Products Using Palladium Catalysts

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